The goal of this project is to study the molecular mechanism by which transforming growth factor-beta (TGF-Beta) induces cell death. TGF-Beta has been shown to be a potent growth-inhibitory factor for cells derived from lymphoid and hematopoietic origins. To investigate and elucidate the molecular mechanism of TGF-Beta signaling pathway that leads to programmed cell death, this proposal seeks to study whether several key players of the TGF-Beta growth inhibitory pathway are involved in TGF-Beta induced apoptosis in leukemic and other cancer cells. Efforts will also be made to identify other unknown molecules which mediate this specific TGF-Beta effect.